Novel phosphine oxides and methods of preparing same



United States Patent 3,116,334 NOVEL PHOSPHINE OXIDES AND METHODS OF PREPARING SAME Sheldon A. Buckler and Martin Epstein, Stamford, Conn., assignors to American Cyanarnid Company, New York, N.Y., a corporation of Maine No Drawing. Filed Apr. 6, 1960, Ser. No. 20,262 21 Claims. (Cl. 260-6065) The present invention relates to novel phosphine oxides and their preparation. More particularly, the instant discovery pertains to the reaction of primary phosphine oxides with carbonyl compounds, i.e., aldehydes and ketones, to produce corresponding secondary and tertiary phosphine oxide derivatives.

The novel phosphine oxides contemplated herein, plus a ready route to these compounds, are a very significant contribution to the art, in view of the fact that the novel oxides are valuable as complexing agents for metal values. Uranyl values, for example, can be selectively leached from an ore containing the same by employing techniques known in the art, as shown by Blake et al. in the Atomic Energy Commission Report O'RNL1903, May 13, 1955. Furthermore, the straightforward, single-step method provided herein affords the very desirable oxides in high purity and good yields.

Pursuant to the instant discovery a primary phosphine oxide is brought into reactive contact with a carbonyl compound, i.e., an aldehyde or a ketone, in the presence of an acid or base and, if desired, in an inert organic solvent medium, such as an alcohol, and the resulting corresponding secondary or tertiary phosphine oxide recovered.

The following equations best illustrate the process contemplated herein:

The characters R, R, R and A in the above formulae have the following meanings: R and R, respectively, represent a member selected from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; cycloalkyl; and phenyl, substituted phenyl; in addition, R equal H; R" is a member selected from the group consisting of H; lower alkyl; and phenyl; and R" taken in conjunction with R may comprise the residue of a cycloalkyl ring; for example, in equation ILI above the carbonyl 3,116,334 Patented Dec. 31, 1963 also represents cyclohexanone; A is a member selected from the group consisting of lower alkylene, monohydroxy-substituted lower alkylene and phenylene.

The novel products of the present invention may be represented by the following generic formula wherein R has the meaning given hereinabove and Z is a member selected from the group consisting of wherein R, R, R and A have the meaning given hereinabove.

Typical primary phosphine oxide reactants useful for preparing the secondary and tertiary oxides of the present discovery are isobutylphosphine oxide, cyclohexylphosphine oxide, octylphosphine oxide, methylphosphine oxide, isopropylphosphine oxide, l-ethylpropylphosphine oxide, cyclopentylphosphine oxide, phenylphosphine oxide, Z-cyanoethylphosphine oxide, dodecylphosphine oxide, allylphosphine oxide, Z-hydroxyethylphosphine oxide, p-chlorophenylphosphine oxide, Z-carbethoxyethylphosphine oxide, and the like. It follows from this representative list of primary phosphine oxide reactants that typical substituents on the R moiety within the purview of the present invention are nitrile, halogen, hydroxy, carbo-lower alkoxy, and the like.

The primary phosphine oxide reactants contemplated herein may be prepared as described in applicants copending U.S. applicant Serial No. 824,169, filed July 1, 1959, which is incorporated herewith by reference.

Representative carbonyl compounds within the generic definitions given hereinabove are benzaldehyde, p-chlorobenzaldehyde, butyraldehyde, 9-hydroxynonanal, p-hy droxybenzaldehyde, S-methoxypentanal, m-nitrobenzaldehyde, 4-octenal, glyoxylic acid, dodecylaldehyde, succinaldehyde, glyoxal, Z-hydroxyadipaldehyde, terephthalaldehyde, isophthalaldehyde, and the like.

As in the case of the primary phosphine oxide reactants, the substituents contemplated herein for the "carbonyl compounds are, typically, halogen, hydroxy, lower alkoxy, nitro, carboxy, and the like.

Referring to Equation I, supra, the aldehyde reactant relative to the primary phosphine oxide reactant is generally present in a molar ratio of at least 2:1. A substantial stoichiometric excess of the carbonyl compound, e.g., on the order of 10:1 or greater, may be employed, however, without deleterious effect. Generally, however, about equivalent or about stoichiometric amounts are used.

The reaction may be carried out in the presence of an acid, preferably a mineral acid, or a base. Typical acids are HBr, HI, H 50 HCl, I I PO HNO and the like, strong organic acids, such as sulfonic and phosphonic acids, e.g., methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, phenylphosphonic acid, and the like. Other similar acids which under the conditions of the reaction are non-oxidizing with respect to the reactants and reaction products are also contemplated.

Typical strong organic and inorganic base catalysts within the purview of the present discovery are triethylamine, heptamethylguanidine, pentametliylguanidine, alkali metal alkoxides, such as sodium methoxide, potassium ethoxide, sodium butoxide, alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide, and the like.

Good results are obtained when reaction is made to take place in the presence of an inert organic solvent. Typical solvents are lower alcohols, such as methanol, ethanol, and the like; others, such as tetrahydrofuran, dioxane, and the like; water; and mixtures of these reactants. Furthermore, any sequence of addition of the reactants may be employed. Likewise, super-atmospheric, sub-atmospheric and atmospheric pressures are contemplated herein.

A wide range of temperatures, on the order of about C. to about 100 C., may be employed. Ambient temperatures C. C.), for example, give very desirable results.

Referring to moiety (a) in Equation II, above, typical lower alkylene groups are methylene, ethylene, trimethylene, propylene, and the like.

Referring to Equations II and II(a), supra, the dialdehyde and the primary phosphine oxide are generally brought together in a ratio of 1:2; however, almost any excess of either reactant relative to the other is contemplated herein. Generally, too great an excess either way is cumbersome and impractical.

The reactants are otherwise brought together under the same conditions given hereinabove for Equation I type reactions, including the use of a solvent.

Referring to Equation III, supra, while the reaction 7 conditions parallel those given hereinabove for Equations I and II, it will be noted that a preferred embodiment involves the use of about equimolar amounts of the reactants. The reaction conditions are otherwise identical with the Equations I and 11 reactions from the standpoint of temperature, mixing sequence, pressure, solvents, etc.

The reactions of Equations IIII above are best carried out in an inert, i.e., non-oxidizing, atmosphere. Several typical ways of doing this involve the use of an atmosphere of N He, H or the like.

The present invention will best be understood by reference to the following examples:

EXAMPLE I Bis(Alpha-Hydroxybenzyl) Isobutylphosphine Oxide A solution of 5.6 grams of isobutylphosphine oxide (0.05 mole), 40 milliliters of methanol, 13.8 grams of benzaldehyde (0.13 mole) and 5 milliliters of concentrated HCl is allowed to stand for 24 hours under nitrogen. A white solid bis(a-hydroxybenzyl)isobutylphosphine oxide precipitates and is colletced. It is recrystallized from acetonitrile and gives a melting point of 157 C.-158 C.

EXAMPLE II Bis( A l pha-H ydroxy-Parachlorobenzyl Cyclohexylphosphine Oxide Bis(Hydr0xymethyl) Octylphosphine Oxide A solution of 6.5 grams of octylphosphine oxide (0.04 mole), dissolved in milliliters of methanol, 8 grams of 37 percent by weight formaldehyde solution (0.1 mole) and 10 milliliters of concentrated HCl is allowed to stand for 2 weeks under nitrogen. The solution is poured onto ice and extracted with chloroform to yield on evaporation bis(hydroxymethyl)octylphosphine oxide.

EXAMPLES IV-VII The following provides further illustrative examples in tabular form. The experimental conditions and work up are identical in every essential respect with Example III. In all cases the catalyst is concentrated HCl.

TABLE I Example Primary Phos- Carbonyl Product Structure phine Oxide Compound C133 tlil) OH IV isopropylphosbenzaldehyde. bis(whydroxybenzyl)isopropyl- CH-P OH phine oxide. phosphine oxide. 3

CH3 OHSOEZ g (IJH V l-ethylpropylp-chlorobenzaldebis(a-hydroxy-p-chloi'obenaylyl- CH P OHC1 phosphine hyde. ethylpropylphosphine oxide. a oxide. CHgCHz l( a VI cyclopeiitylphosbutyi'aldehyde bis(l-hyd 'oxybutyl)eyclopentyl- -CHCHiCHzCH 1 phine oxide. phosphine oxide.

t t 1 VII phenylphosphine Q-hydroxynonanal. bis(1,Q-dihydroxynonyDphenyl- P -CH(CH2)7CH OII g oxide. phosphine oxide.

t r VIII... cyanoethylphosp-hydroxybenzbis(a-hydroxy-p-hydroxybenzyl)- CNOHzCHg-P 'CHOH phine oxide. aldehyde. cyanoethylphosphme oxide. 1

t t 1 IX dodeeylpliosphi'ne omethoxypenbis(.l-hydi-oxy-5-methoxy-pentyl)- OH3(CH P CH(OH2)aCH OMe oxide. tanal. dodeeylphosphine oxide.

.TABLE I-Ontinued Example Primary Phos- Carbonyl Product Structure phine Oxide Compound N02 i i X allylphosphine m-nitrobenzaldebis(whydroxy-m-nitrophenyl)- CHFCHCHQP -CH oxide. hyde. allylphosphine oxide. 2

XI p-ehlorophenyli-oetenal bis(l-hydroxy--octenyl)-p-ehloro- Cl-P CH(CH )ZCH=CH(CH )ZOH 2 phosphine oxide. phenylphosphine oxide.

t r l XII octylphosphine dodecylaldehyde. bis(l-hydroxydodecyl)octylphosoctyl-P CH(CHz) uCH z oxide. phine oxide.

EXAMPLE XIII Bis (Alpha-Hydroxybenzyl)Isobutylphosphine Oxide The procedure of Example I, above, is repeated in every essential respect with the exception that 1 gram of sodium methoxide is used in place of the concentrated HCl. The same product is obtained.

EXAMPLE XIV Bis (A lpha-lzydroxy-parachl0robenzyl Cyclohexylphosphine Oxide The procedure of Example II, above, is repeated in every essential respect with the exception that 1 gram of triethylamine is used in place of the concentrated HCl. The same product is obtained.

EXAMPLE XV Bis(Hydroxymethyl)Octylphosphine Oxide The procedure of Example III, above, is repeated in every essential respect with the exception that 2 milliliters of heptamethylguanidine is used in place of the concentrated HCl. The same product is obtained.

EXAMPLE XVI 1,Z-Dihydroxyethylene-Bis(Octylphosphine Oxide) A solution of grams of octylphosphine oxide (0.062 mole) is dissolved in 40 milliliters of methanol, 6.3

grams of 30 percent by weight glyoxal solution (0.033 mole) and 5 milliliters concentrated HCl is allowed to stand at room temperature under nitrogen for one day. The solid (5.5 grams) that separates is filtered and identified as 1,2 dihydroxyethylene bis (octylphosphine oxide) in 44 percent by Weight of the theoretical yield. The solid is recrystallized from acetic acid to give material having a melting point of 194 C.196 C.

EXAMPLE XVII 1,5-Dihydr0xypenzamethylene-Bis(Octylphosphine Oxide) EXAMPLES XVIII-XXIII The following provides further illustrative examples in tabular form. The experimental conditions and work up are the same in every essential respect as Example XVI, above.

TABLE II Example Primary Phosphine Dialdehyde Product Structure Oxide I R R i XVIII octylpliosphine suceinaldehyde.. 1,4-dihyrdoxytetramethylenecoty1PCH(OH CHP-octyl oxide. bis(octylpl1osphine oxide). I

H H i t 9 I XIX isobutylphosglyoxal 1,2-dihydroxyethyleneisobutylP-CHCIIPisobutyl phine oxide. bisfisobutylphosphine I oxide). H H

(I? (?H |OH (I? XX phonylphosglyoxal 1,2-dihydroxyethylene-bisphenyl-P-CIICHI pheny1 phine oxide. (phinylphosphine oxide).

fl) (|)II (|)II OH (1? XXI... cyelohcxylphos- 2-l1ydroxy- 1,2,6-tzihydroxyhexarnethy- PCH-CI-I(CH 3HP phine oxide. adipaldohyde. lone bis(cyclohexylphos- I I phine oxide). H H

i i i i XXII 2-cyanoethyitoreplithalaldea,a-dihydroxy-1,4-xylylene- CNCHzCIIzP-CI'I CH-PCH CH CN phosphine liyde. l)is(2-cyanoethylphosphine I I oxide. oxide). II H I i i r XXIII. p-chloropheny1 isophthalaldea,zx'- dihydroxy 1,3 OI POH phosphine hyde. xylylene bis(p chloro- I oxide. pheuylphosphine oxide). H

EXAMPLE XXIV 1,Z-Dihydroxyethylene-Bis(Octylphosphine Oxide) The procedure of Example XVI, above, is repeated in while the present invention has been described in .detail with respect to specific embodiments thereof, it is not intended that these details be construed as limitations upon the scope of the invention, except insofar as they every essential respect with the exception that 2 milli- 5 appear i th appended cl i s, liters of pentamethylguanidine is used in place of con- W l i Centfated The Same Product is Obtained- 1. A phosphine oxide conforming to the formula EXAMPLE XXV O 1,5-Dihydr0xypentamethylane-Bis(Octylphosphine ll RP z Oxide) The procedure of Example XVII, above, is repeated n every essential res ect w th the exception that 1.5 gr wherein Z represents a member selected from the group of potassium hydroxide is used In place of the concen- Consisting of trated HCl. The same product is obtained.

EXAMPLE XXVI f f t,

. o- R' CAC-P=R I-Hydroxycyclohexyloctylphosphme Oxide OH OH OH H A solutlon of 4.9 grams of octylphosphine oxide (0.03 mole) dissolved in milliliters of ethanol, 7.0 grams cyclohexanone (0.07 mole) and 12 milliliters concen- C-R H trated HCl is refluxed for 4 hours under nitrogen. The solvent is evaporated at reduced pressure and the remaining gum triturated with ether to yield 2.7 grams of 1-hy- H 0 25 droxycyclohexyloctylphosphme oxrde 1n percent by O C P R 0 weight yield. The solid is recrystallized from ethanol to 6 give a melting point of 101 C.-103 C.

EXAMPLES XXVII-XXXI \H The following provides further illustrative examples in 30 tabular form. The conditions and work up are similar Whefeln in every essential respect to Example XXVI, above. R in the above formulae represents a member selected TABLE III Example Primary Phosphine Oxide Carbonyl Compound Product Structure 0113 (H) (1)11 CH3 XXVIL. eyelohexylphosphine oxide =0 l-hydroxy-l-methyl ethylcyclohexyl- O-P-Ofi phosphine oxide. CH H CH r r e XXVIII. 2-cyanoethylphosphine -CCH3 zx-hydroxy-a-methylbenzyLZ-cyano- CNCH2CH3PCH oxide. ethylphosphine oxide.

H CH CH3CH2OH2 (H) (|)H CI'I1CH2CH3 XXIX--. phenylphosphine oxide o=o 1-hydroxy- -p py1 y p e y p os- P-0H phine oxide. l CHaCHzCHg H CHzCHgCHa Cga fi (|)H XXX isobutylphosphine oxide @OHO whvdiroxybenzylisobutylphosphine /OHCH;I]CH

OH; H

1? E XXXI.-. eyclohexylphosphine oxide OH3OH2CH20HO l-hydoxybutylcyclohexylphosphine C -1I HOHzCHgCHa OX1 e.

(H) OH XXXIL- butylphosphineoxide CH (CHz)mCHO l-hydoxydodecylbutylphosphine OH CHzCH Cl-I lf-fi(CHQ CH OX1 G.

H r R XXXIIL octylphosphine oxide HOHO 1hyggoxymethyloctylphosphine oety1I|-CH,

OX1 e.

EXAMPLE XXXIV 1-Hydroxycyclohexyloctylphosphine Oxide The procedure of Example XXV is repeated in every essential respect with the exception that 2 grams of sodium hydroxide are used in place of the concentrated HCl. The same product is obtained.

Clearly, the instant discovery encompasses numerous modifications within the skill of the art. Consequently,

from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; cycloalkyl; phenyl and substituted phenyl; said substituents for alkyl, alkenyl and phenyl represented by R being selected from the group consisting of nitrile, halogen, hydroxy and carbo-lower alkoxy;

R" represents a member selected from the group consisting of hydrogen; lower alkyl; and phenyl;

R represents a member selected from the group consisting of alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; phenyl and substituted phenyl; said substituents for alkenyl and phenyl being selected from the group consisting of halogen, hydroxy, lower alkoxy, nitro and carboxy; however, when R is selected from the group consisting of said phenyl and said substituted phenyl, R is phenyl;

A is a member selected from the group consisting of lower alkylene, monohydroxy-substituted lower alkylene and phenylene.

2. Bis(alpha-hydroxybenzyl)isobutylphosphine oxide.

3 Bis alpha-hydroxy-parachlorobenzyl cyclohexylphosphine oxide.

4. 1,Z-dihydroxyethylene-bis(octylphosphine oxide).

5 1,5 -dihydroxypentamethylene-bis (octylphosphine oxide).

6. A method of preparing a tertiary oxide conforming to the formula 0 II niche) 6H which comprises bringing into reactive contact a primary phosphine oxide corresponding to the formula and an aldehyde conforming to the formula R'CHO in the presence of a member selected from the group consisting of an acid and a base and recovering the resulting tertiary phosphine oxide,

R in the above formulae represents a member selected from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; cycloalkyl; phenyl and substituted phenyl; R represents a member selected from the group consisting of H and the members represented by R, above; and substituents for the alkyl, alkenyl and phenyl members of R, above, being selected from the group consisting of nitrile, lower alkoxy, halogen, hydroxy, and carboxy; and said substituents for alkyl, alkenyl and phenyl members of R, above, being selected from the group consisting of halogen, hydroxy, lower alkoxy, nitro and carboxy. 7. The process of claim 6 wherein the catalyst is a mineral acid.

8. The process of claim 6 wherein the catalyst is a base.

9. The process of claim 6 wherein the reactants are present in about equimolar proportions.

10. A method of preparing secondary phosphine oxides corresponding to the formula if bi FR HOH OHI-I which comprises bringing together into reactive contact a primary phosphine oxide corresponding to the formula and a dialdehyde conforming to the formula OHC--A-CHO said reactants being brought together in the presence of a catalyst selected from the group consisting of an acid and a base, and recovering the resulting secondary phosphine oxide.

R in the above formulae representing a member selected from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; cycloalkyl; phenyl and substituted phenyl; said substituents for alkyl, alkenyl and phenyl, above, being selected from the group consisting of nitrile, lower alkoxy, halogen, hydroxy and carboxy, A being a member selected from the group consisting of lower alkylene, monohydroxy-substituted lower alkylene and phenylene. 11. The process of claim 10 wherein the catalyst is a mineral acid.

12. The process of claim 10 wherein the catalyst is a base.

13. The process of claim 10 wherein the reactants are present in about equimolar proportions.

14. A method of preparing secondary phosphine oxides corresponding to the formula which comprises bringing together into reactive contact a primary phosphine oxide conforming to the formula and glyoxal, said reactants being brought together in the presence of a catalyst selected from the group consisting of a base and an acid, and recovering the resulting secondary phosphine oxide,

R in the above formulae representing a member se lected from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkenyl having from 1 to 18 carbon atoms, branched and straight chain; cycloalkyl; phenyl and substituted phenyl; said substituents for alkyl, alkenyl and phenyl, above, being selected from the group consisting of nitrile, lower alkoxy, halogen, hydroxy and carboxy.

15. The process of claim 14 wherein the catalyst is a mineral acid.

16. The process of claim 14 wherein the catalyst is a base.

17. The process of claim 14 wherein the reactants are present in equimolar proportions.

18. A method of preparing secondary phosphine oxides corresponding to the formula which comprises bringing together into reactive contact a primary phosphine oxide conforming to the formula ll R-PHz and a carbonyl compound corresponding to the formula /C=O R 5 said reactants being brought together in the presence of a member selected from the group consisting of an acid and a base,

R in the above formulae represents a member selected from the group consisting of alkyl having from 1 to 18 carbon atoms, branched and straight chain, alkenyl having from 1 to 18 carbon atoms, branched and straight chain, substituted alkyl having from 1 to 18 carbon atoms, branched and straight chain, substi- H and the same members represented by R, above, said substituents for alkyl, alkenyl and phenyl represented by R, however, being selected from the group consisting of halogen, hydroxy, lower alkoxy, nitro and carboxy; R" is a member selected from the group consisting of H, lower alkyl, and phenyl, and R taken in conjunction with R also represents the remainder of a cycloalkyl ring.

19. The process of claim 18 wherein the catalyst is a 10 mineral acid.

20. The process of claim 18 wherein the catalyst is a base.

21. The process of claim 18 wherein the reactants are present in equimolar proportions.

tuted alkenyl having from 1 to 18 carbon atoms, 15

'branched and straight chain; cycloalkyl; phenyl and References Cited in the filfi Of this Patent substituted phenyl; said substituents for alkyl, alke- UNITED STATES PATENTS nyl and phenyl being selected flrlom the group consist- 2,584,112 Brown Feb 5 1952 e Of q lower alkoxy, alogen, y q y and 3,005,029 Buckler et a1 Oct 17, 1961 carboxy; R 1s a member of the group consisting of 20 

1. A PHOSPHINE OXIDE CONFORMING TO THE FORMULA 